Study Description

Brief Summary:

This is a Phase 2, multi-center, randomized, double-blind, placebo-controlled, proof-of-principle study of neflamapimod versus matching placebo (randomized 1:1) administered with food for 16 weeks in subjects with DLB. The primary objective is to evaluate the effect of neflamapimod on cognitive function as assessed in a study-specific Cogstate Neuropsychological Test Battery (NTB). Secondary endpoints include the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB), Mini-Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI-10), Timed Up and Go Test, and electroencephalogram (EEG) as a potential biomarker for DLB.

Condition or disease	Intervention/treatment	Phase
Dementia With Lewy Bodies (DLB)	Drug: Neflamapimod	Phase 2

Study Design

Layout table for study information

Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	80 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	A Double-Blind, Placebo-Controlled 16-Week Study of the Cognitive Effects of Oral p38 Alpha Kinase Inhibitor Neflamapimod in Dementia With Lewy Bodies (DLB)
Actual Study Start Date :	September 30, 2019
Estimated Primary Completion Date :	June 2020
Estimated Study Completion Date :	June 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Neflamapimod 40 mg capsules administered orally, BID or TID with food for 16 weeks; subjects will follow the BID regimen if weighing <80 kg or the TID regimen if weighing ≥80 kg	Drug: Neflamapimod Double-Blind, Placebo-Controlled
Placebo Comparator: Placebo 40 mg matching placebo capsules administered orally, BID or TID with food for 16 weeks; subjects will follow the BID regimen if weighing <80 kg or the TID regimen if weighing ≥80 kg	Drug: Neflamapimod Double-Blind, Placebo-Controlled

Outcome Measures

Primary Outcome Measures :

Composite score of a study-specific Cogstate Neurological Test Battery (NTB) including the Cogstate Letter Fluency Test and Category Fluency Test [ Time Frame: 16 weeks ]
Change from Baseline to Week 16 in the composite score of a study-specific Cog-state Neurological Test Battery (NTB), including assessments of attention, executive function, and visuospatial function in neflamapimod treated-subjects as compared to the placebo-treated subjects, as analyzed using the Mixed Model Repeated Measures (MMRM) analysis method. The following six tests will be included in the composite: (1) Cogstate Detection test (DET), (2) Cogstate Identification test (IDN), (3) Cogstate One Card Learning test (OCL), (4) Cogstate One Back test (ONB), (5) Letter Fluency Test, (6) Category Fluency Test (CFT). Each score on the individual tests will be converted to a z-score, and then a total z-score will be calculated, in which each test is weighted equally. The change in total z-score in neflamapimod vs. placebo-recipients will be analyzed. As the analysis is based on z-scores, there is no minimum or maximum value.

Secondary Outcome Measures :

Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) [ Time Frame: 16 weeks ]
Change in Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) score based on semi-quantitative scoring of each domain (box) evaluating cognitive impairment in milder and more progressive forms of dementia, in neflamapimod-treated subjects compared to placebo-recipients. The domain (box) scores will be calculated for a Sum of Boxes score. Secondary efficacy endpoints will utilize the same analysis method and model as the primary endpoint.
Mini-Mental State Examination (MMSE) [ Time Frame: 16 weeks ]
Change in Mini-Mental State Examination (MMSE) with respect to orientation, memory, concentration, language, and praxis (scores ranging from 0 to 30 with lower scores indicating greater cognitive impairment), in neflamapimod-treated subjects compared to placebo-recipients. Secondary efficacy endpoints will utilize the same analysis method and model as the primary endpoint.
Neuropsychiatric Inventory (NPI-10) [ Time Frame: 16 weeks ]
Change in Neuropsychiatric Inventory (NPI-10) domains, specifically depression (dysphoria), anxiety, hallucinations, and agitation/aggression, in neflamapimod-treated subjects compared to placebo-recipients. Responses indicating subject has a problem with a particular sub-domain lead to questions of the caregiver rating the frequency of the symptoms on a 4-point scale, severity on a 3-point scale, and the distress the symptoms cause them on a 5-point scale. Secondary efficacy endpoints will utilize the same analysis method and model as the primary endpoint.
International Shopping List Test (ISLT) [ Time Frame: 16 weeks ]
Change in International Shopping List Test (ISLT) immediate and delayed recall and recognition will be used to assess episodic memory in neflamapimod-treated subjects compared to placebo-recipients. Secondary efficacy endpoints will utilize the same analysis method as the primary endpoint.
Timed Up and Go Test (TUG) [ Time Frame: 16 weeks ]
Change in Timed Up and Go Test (TUG) to assess mobility (score of >15 seconds indicates subject has increased risk of falls) in neflamapimod-treated subjects compared to placebo-recipients. Secondary efficacy endpoints will utilize the same analysis method and model as the primary endpoint.
Quantitative Electroencephalogram (qEEG) [ Time Frame: 16 weeks ]
Change in quantitative electroencephalogram (qEEG) parameters (all waveforms, with particular focus on relative alpha and theta power) with the subject awake in accordance with the 10-20 International System of Electrode placement will be evaluated as a potential biomarker for DLB. Slowing of the dominant frequency band by qEEG over posterior aspects of the brain has been recognized to be prominent in DLB, and various patterns have been identified to differentiate DLB from AD. EEG will be analyzed at an academic center (VU Medical Center, Amsterdam), who will develop the specific parameters during the conduct of the study, and they will specify the analytic approach in the Statistical Analysis Plan (SAP) that will be implemented prior to the completion of subject enrollment.

Eligibility Criteria

Layout table for eligibility information

Ages Eligible for Study:	55 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Men and women aged ≥55 years.
Subject or subject's legally authorized representative is willing and able to provide written informed consent.
Probable DLB and identified cognitive deficits, according to current consensus criteria (McKeith et al, 2017), specifically one core clinical feature and a positive DaTscan. If a negative DaTscan, but the subject has historical PSG-verified RBD, the subject would also qualify.
MMSE score of 15-28, inclusive, during Screening.
Currently receiving cholinesterase inhibitor therapy, having received such therapy for greater than 3 months and on a stable dose for at least 6 weeks at the time of randomization. Except for reducing the dose for tolerability reasons, the dose of cholinesterase inhibitor may not be modified during the study.
Normal or corrected eye sight and auditory abilities, sufficient to perform all aspects of the cognitive and functional assessments.
No history of learning difficulties that may interfere with their ability to complete the cognitive tests.
Must have reliable informant or caregiver.

Exclusion Criteria:

Diagnosis of any other ongoing central nervous system (CNS) condition other than DLB, including, but not limited to, post-stroke dementia, vascular dementia, Alzheimer's disease (AD), or Parkinson's disease (PD).
Suicidality, defined as active suicidal thoughts within 6 months before Screening or at Baseline, defined as answering yes to items 4 or 5 on the C-SSRS, or history of suicide attempt in previous 2 years, or, in the Investigator's opinion, at serious risk of suicide.
Ongoing major and active psychiatric disorder and/or other concurrent medical condition that, in the opinion of the Investigator, might compromise safety and/or compliance with study requirements.
Diagnosis of alcohol or drug abuse within the previous 2 years.
Poorly controlled clinically significant medical illness, such as hypertension (blood pressure >180 mmHg systolic or 100 mmHg diastolic); myocardial infarction within 6 months; uncompensated congestive heart failure or other significant cardiovascular, pulmonary, renal, liver, infectious disease, immune disorder, or metabolic/endocrine disorders or other disease that would interfere with assessment of drug safety.
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2 × the upper limit of normal (ULN), total bilirubin >1.5 × ULN, and/or International Normalized Ratio (INR) >1.5.
Known human immunodeficiency virus, hepatitis B, or active hepatitis C virus infection.
Participated in a study of an investigational drug less than 3 months or 5 half-lives of an investigational drug, whichever is longer, before enrollment in this study.
History of previous neurosurgery to the brain.
If male with female partner(s) of child-bearing potential, unwilling or unable to adhere to contraception requirements specified in the protocol.
If female who has not has not reached menopause >1 year previously or has not had a hysterectomy or bilateral oophorectomy/salpingo-oophorectomy, has a positive pregnancy test result during Screening and/or is unwilling or unable to adhere to the contraception requirements specified in the protocol.

Contacts and Locations

Locations

Show 24 study locations

Layout table for location information

United States, California
University of California San Diego (UCSD)
La Jolla, California, United States, 92037
Pacific Neuroscience Institute
Santa Monica, California, United States, 90404
United States, Colorado
University of Colorado
Aurora, Colorado, United States, 80045
United States, Florida
Elite Clinical Research
Miami, Florida, United States, 33144
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States, 66103
United States, Massachusetts
Massachusetts General Hospital
Charlestown, Massachusetts, United States, 02129
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48105
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Nevada
Cleveland Clinic - Lou Ruvo Center for Brain Health
Las Vegas, Nevada, United States, 89106
United States, New York
New York Presbyterian Hospital - Columbia University Medical Center
New York, New York, United States, 10032
University of Rochester
Rochester, New York, United States, 14618
United States, North Carolina
University of North Carolina
Chapel Hill, North Carolina, United States, 27599
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
The Ohio State University
Columbus, Ohio, United States, 43210
United States, Oregon
Summit Research Network
Portland, Oregon, United States, 97210
Oregon Health & Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19107
United States, Virginia
University of Virginia
Charlottesville, Virginia, United States, 22908
National Clinical Research, Inc.
Richmond, Virginia, United States, 23294
United States, Washington
Northwest Clinical Research Center
Bellevue, Washington, United States, 98007
University of Washington
Seattle, Washington, United States, 98104
Inland Northwest Research
Spokane, Washington, United States, 99202
Netherlands
Brain Research Center
Amsterdam, Netherlands
Brain Research Center
Den Bosch, Netherlands

Sponsors and Collaborators

EIP Pharma Inc

Worldwide Clinical Trials

Investigators

Layout table for investigator information

Study Director:	John Alam, MD	EIP Pharma

免费获得国外治疗治疗痴呆相关药品，最快 1 个工作日回馈药物信息

Cognitive Effects of Oral p38 Alpha Kinase Inhibitor Neflamapimod in Dementia With Lewy Bodies (AscenD-LB)

study details

table view